Research: Membrane biogenesis and transport In certain cell types particle envelopment can consume up to 30% of cellular membrane pools and a large fraction of these membranes is provided at the expense of endosomes. In response to this re-appropriation of organelles, cells synthesize new membranes within a few hours. During phagocytosis organelle biogenesis can thus be studied in relative isolation and we are asking how the synthesis of lipids and endosomal proteins is controlled and coordinated. Following phagocytosis, the resulting vacuole or "phagosome" fuses with lysosomes. These vesicles contain digestive enzymes, toxic peptides and other molecules that are required for killing and digestion for example of phagocytosed bacteria. A second aspect of our research is concerned with the mechanisms by which lysosomes are targeted to phagosomes and the question of how these interactions are controlled under specific physiological circumstances.
Selected Publications: Stockinger W, Nohturfft A. (2008) Studying phagocytosis by live-cell scintillation proximity assay. Methods Mol Biol. 2008;440:147-55. PMID: 18369943. [web page] [pdf] Trivedi, V, Zhang, SC, Stockinger, W and Nohturfft, A. (2007) A cell-free scintillation proximity assay for studies on lysosome-to-phagosome targeting. Sci. STKE 2007, pl3. [web page] [pdf] Trivedi, V., Zhang, S. C., Castoreno, A. B., Stockinger, W., Shieh, E. C., Vyas, J. M., Frickel, E. M. and Nohturfft, A. (2006). Immunoglobulin G Signaling Activates Lysosome/Phagosome Docking. Proc. Natl. Acad. Sci. USA 103: 18226-18231. [web page] [pdf] [MCB News article] Stockinger W, Zhang SC, Trivedi V, Jarzylo LA, Shieh EC, Lane WS, Castoreno AB, Nohturfft A. (2006) Differential Requirements for Actin Polymerization, Calmodulin, and Ca2+ Define Distinct Stages of Lysosome/Phagosome Targeting. Mol Biol Cell. Feb 1; 17, 1697–1710. [web page] [pdf] Castoreno AB, Wang Y, Stockinger W, Jarzylo LA, Du H, Pagnon JC, Shieh EC, Nohturfft A. (2005). Transcriptional regulation of phagocytosis-induced membrane biogenesis by sterol regulatory element binding proteins. Proc. Natl. Acad. Sci. U S A. 102, 13129-13134. [web page] [pdf] [MCB News article] Wang Y, Castoreno AB, Stockinger W, Nohturfft A. (2005). Modulation of endosomal cholesteryl ester metabolism by membrane cholesterol. J. Biol. Chem. 280, 11876-86. [web page] [pdf] Stockinger W, Castoreno AB, Wang Y, Pagnon JC, Nohturfft A. (2004). Real-time analysis of endosomal lipid transport by live cell scintillation proximity assay. J. Lipid Res. 45, 2151-8. [pdf] Nohturfft, A., and Losick, R. (2002). CELL BIOLOGY: Fats, Flies, and Palmitate. Science 296, 857-858. [pdf] Nohturfft, A., Yabe, D., Brown, M.S., and Goldstein, J.L., and Espenshade, P.J. (2000) Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. Cell 102, 315-323. [web page] [pdf] Nohturfft, A., DeBose-Boyd, R., Scheek, S., Brown, M.S., and Goldstein, J.L. (1999) Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi. Proc. Natl. Acad. Sci. U.S.A. 96, 11235-11240. [web page] [pdf] Nohturfft, A., Brown, M.S., and Goldstein, J.L. (1998) Sterols regulate processing of carbohydrate chains of wild-type SREBP cleavage-activating protein (SCAP), but not sterol-resistant mutants Y298C or D443N. Proc. Natl. Acad. Sci. U.S.A. 95, 12848-12853. [web page] [pdf] Nohturfft, A., Brown, M.S., and Goldstein, J.L. (1998) Topology of SREBP Cleavage-Activating Protein, a polytopic membrane protein with a sterol-sensing domain. J. Biol. Chem. 273, 17243-17250. [web page] [pdf] Nohturfft, A., Hua, X., Brown, M.S., and Goldstein, J.L. (1996) Recurrent G-to-A substitution in a single codon of SREBP cleavage-activating protein causes sterol resistance in three mutant Chinese hamster ovary cell lines. Proc. Natl. Acad. Sci. U.S.A. 93, 13709-13714. [web page] [pdf]
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